The ongoing worldwide obesity epidemic is creating enormous heath consequences, including increased type-2 diabetes, cancer, and heart disease. Metabolic syndrome is a pernicious complication that affects many, but not all, obese individuals and greatly increases the likelihood of such diseases. Although drug treatments exist, the cost to treat all obese individuals would be prohibitive. Therefore, a critical public health need exists for instruments that provide early diagnosis of metabolic syndrome and enable cost-effective treatment. The long-term goal is to develop technologies that detect metabolic activity in humans for research and clinical applications. The chemical currency of energy and metabolism is adenosine triphosphate (ATP), produced by enzyme complexes within mitochondria. Preliminary work suggests that such complexes generate harmonics in response to oscillatory electric fields. The focus of this proposal is to develop sensors, based on harmonic generation spectroscopy, which detect metabolic activity in mitochondria. The specific aims are to: (1) develop sensors that detect activity of mitochondrial complexes in cells in vitro; (2) determine which features of the harmonic spectra correlate with activity of specific enzyme complexes;and (3) assess the viability of detecting metabolic syndrome in obese patients. This approach will enable eventual development of clinical devices that can detect metabolic syndrome early or monitor resting and active metabolism.